%0 Journal Article
%T CXCR6+CD69+ CD8+ T cells in ascites are associated with disease severity in patients with cirrhosis.
%A Niehaus C
%A Klein S
%A Strunz B
%A Freyer E
%A Maasoumy B
%A Wedemeyer H
%A Björkström NK
%A Kraft ARM
%A Cornberg M
%J JHEP Rep
%V 6
%N 6
%D 2024 Jun
%M 38882602
%F 9.917
%R 10.1016/j.jhepr.2024.101074
%X UNASSIGNED: Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and may eventually lead to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we analyzed the role of CD8+ T cells in the ascites immune compartment.
UNASSIGNED: Peripheral blood and ascites fluid were collected from 50 patients with decompensated cirrhosis. Phenotype and functional responses of CD8+ T cells were analyzed, and obtained data were compared with each other as well as with healthy controls and patients with compensated cirrhosis.
UNASSIGNED: High-dimensional flow cytometry revealed that CD8+ T cells are abundant in the ascites of patients with cirrhosis and exhibit a chronically activated bystander phenotype with innate-like functions. Indeed, we identified distinct CXCR6+CD69+ clusters of late effector memory CD8+ T cells that were rarely found in blood and correlated with clinical parameters of disease severity. Moreover, this CD8+ T-cell population was hyperresponsive to innate cytokines and exhibited cytokine-mediated bystander activation. Interestingly, the Janus kinase (JAK) inhibitor tofacitinib was able to effectively block bystander-activated CXCR6+CD69+ CD8+ T cells and significantly suppress effector molecule production.
UNASSIGNED: The results indicate that CXCR6+CD69+ CD8+ T cells in ascites are associated with disease severity and may contribute to inflammation in patients with decompensated cirrhosis, suggesting that targeted inhibition of this immune cell subset may be a viable therapeutic option.
UNASSIGNED: Patients with advanced cirrhosis often develop hepatic decompensation, which is accompanied by systemic inflammation and eventually leads to acute-on-chronic liver failure. One important cause of systemic hyperinflammation is a dysregulated overshooting immune response in ascites in the abdominal cavity. In this study, we demonstrate that CXCR6+CD69+ CD8+ T cells are abundant in the ascites of patients with cirrhosis, exhibit a chronically activated bystander phenotype, and correlate with clinical parameters of disease severity. Moreover, we show that the Janus kinase (JAK) inhibitor tofacitinib can effectively block these bystander-activated CXCR6+CD69+ CD8+ T cells, suggesting that targeted inhibition of this immune cell subset may be a potential therapeutic strategy.
UNASSIGNED: Prospective registry: INFEKTA (DRKS00010664).